The measurement of triglycerides in clinical chemistry is important as an indicator of the presence of pancreatic disease, hyperlipidemia, coronary artery occlusive disease, etc. In the clinical laboratory, in order to have confidence in these measurements a quality control system needs to be in place. Controls, calibrators, and standards are integral components of this quality control system and well known to those in the clinical chemistry field ( see pg 430, Textbook of Clinical Chemistry, by N. W. Tietz, W. B. Saunders Co., 1986). There is considerable literature on the use of triglycerides for controls, calibrators, and standards. These triglycerides include those extracted from egg yolk, purified olive oil (triolein) or others isolated from animal or human blood. However, there are inherent difficulties in using these materials in multiconstituent controls, calibrators or standards such as:
1. They are unstable to freeze-thaw processing. PA1 2. They can precipitate, and this precipitation can concomitantly affect other analytes such as calcium and phosphate. PA1 3. They tend to become easily and quickly contaminated by microbes, such contamination adversely affecting the products in which they are used. PA1 4. They are usually poorly characterized mixtures causing reproducibility problems. PA1 5. Their assayed values are not stable and continue to rise over time. PA1 6. Some are too insoluble in protein solutions to be useful (controls, calibrators, or standards commonly contain triglyceride levels as high as 400 mg/dl).
Some clinical chemistry control manufacturers attempt to circumvent these difficulties by substituting glycerol for the triglyceride to mimic the chemistry of the true triglyceride. This approach has met with limited success because the hydrolysis step which is essential in certain assays is eliminated, and, for some assays requiring measurement of hydrolyzed fatty acids, glycerol is totally unsuitable.
Manufacturers could theoretically use synthetic triglyceride analogs such as, 2,3-dimercaptopropan-1-ol tributyrate, beta-naphthyl laurate, beta-naphthyl myristate, phenyl laurate and sorbitan esters, methylumbelliferone- and N-methylindoxyl myristate as components in controls, calibrators, or standards, but these materials are vastly too expensive and/or insoluble in a protein matrix to be practically useful. Normally, aqueous insoluble triglycerides are insufficiently soluble to be practically used in clinical controls. They can sometimes be made soluble by the use of a surfactant, but the surfactant often adversely affects other constituents, e.g. enzymes.
This invention relates to the new and innovative use of existing material as substitutes for human, animal or egg yolk triglycerides in multiconstituent clinical chemistry controls, calibrators, standards and related preparations. The substitute materials include medium carbon length (e.g. C.sub.8, C.sub.10, C.sub.18) fatty acids esterified to glycerol to form mono- and di-glyceride mixtures, which are currently commercially used as vehicles for water-insoluble, oil-soluble pharmaceuticals and as emollient oils for facial creams and cosmetics. They are sufficiently soluble in protein solutions and yield stable triglyceride measurements on standing, without extraneous additional stabilizers required in other preparations. Similar materials which can also be used include, but are not limited to, glycerol tripropionate, and glyceryl tributrate. The use of these materials has avoided the problems of freeze-thaw instability, precipitation, microbial contamination, and poor characterization (and hence reproducibility) which are encountered with the previous materials. These new materials also are much less expensive to use than the previous materials and methods, thus making them practical for use in the manufacture of the multiconstituent clinical control materials. The invention covers not only the identification of the material but also techniques for its use.